During development, tissues are sculpted into organs with precise forms and functions in a process called tissue morphogenesis. Tissue morphogenesis results from cellular forces that are transmitted across the tissue. Improper generation or coordination of forces leads to defects in organ formation, such as neural tube defects. Abnormal activation of pathways that generate cellular forces and drive cell shape change can promote cancer cell metastasis. Therefore, it is critical to both our understanding of development and human disease to determine the mechanisms that control tissue morphogenesis at the molecular, cellular, and tissue level. Tissue invagination during gastrulation and neural tube closure is driven by apical constriction of epithelial cells. This causes columnar cells to adopt a wedge shape, which promotes folding of the epithelial sheet. We made the surprising discovery that apical constriction during Drosophila gastrulation is driven by pulsed contractions and subsequent stabilization of the actin-myosin cytoskeleton. Contraction pulses have now been observed to promote many different morphogenetic processes, including tissue contraction, convergent extension, and axis elongation. The molecular mechanisms responsible for this dynamic contraction and how contractile force is transmitted and coordinated across the tissue is unknown. The availability of live imaging, quantitative image analysis, genetics (mutants, RNAi), cell biology (drugs), biophysics (laser cutting), and biochemistry makes Drosophila gastrulation a powerful system to address these questions. We will investigate how forces propagate from the molecular to the tissue level. First, we will determine the function of myosin motor activity and actin filament depolymerization during pulsatile contraction. Second, we will examine how contractile forces are transmitted between cells to generate epithelial tension. Third, we will determine how biochemical and mechanical signals regulate the coordination of cell shape across the tissue and whether pulsation is critical for this coordination. This multidisciplinary and multiscale approach is essential to understand how dynamic molecular and cellular behaviors collectively result in precise changes in tissue morphology. Members of my lab have backgrounds in cell biology, genetics, physics, and computer science. In addition, we have established collaborations with computational biophysicists and a functional genomics lab to expand our research capabilities. We are poised to make important discoveries regarding the molecular and cellular mechanisms that drive tissue morphogenesis.
Understanding mechanisms of tissue morphogenesis is fundamental to understanding birth defects and cancer progression. We will undertake a multidisciplinary approach to examine how mechanical forces are generated and transmitted between cells to sculpt tissues during development. These studies promise to provide insight into how molecular and cellular behaviors are regulated and coordinated during development.
|Vasquez, Claudia G; Martin, Adam C (2016) Force transmission in epithelial tissues. Dev Dyn 245:361-71|
|Coravos, Jonathan S; Mason, Frank M; Martin, Adam C (2016) Actomyosin Pulsing in Tissue Integrity Maintenance during Morphogenesis. Trends Cell Biol :|
|Jodoin, Jeanne N; Martin, Adam C (2016) Abl suppresses cell extrusion and intercalation during epithelium folding. Mol Biol Cell 27:2822-32|
|Xie, Shicong; Martin, Adam C (2015) Intracellular signalling and intercellular coupling coordinate heterogeneous contractile events to facilitate tissue folding. Nat Commun 6:7161|
|Rodal, Avital A; Del Signore, Steven J; Martin, Adam C (2015) Drosophila comes of age as a model system for understanding the function of cytoskeletal proteins in cells, tissues, and organisms. Cytoskeleton (Hoboken) 72:207-24|
|Jodoin, Jeanne N; Coravos, Jonathan S; Chanet, Soline et al. (2015) Stable Force Balance between Epithelial Cells Arises from F-Actin Turnover. Dev Cell 35:685-97|
|Chanet, Soline; Martin, Adam C (2014) Mechanical force sensing in tissues. Prog Mol Biol Transl Sci 126:317-52|
|Martin, Adam C; Goldstein, Bob (2014) Apical constriction: themes and variations on a cellular mechanism driving morphogenesis. Development 141:1987-98|
|Vasquez, Claudia G; Tworoger, Mike; Martin, Adam C (2014) Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis. J Cell Biol 206:435-50|
|Mason, Frank M; Tworoger, Michael; Martin, Adam C (2013) Apical domain polarization localizes actin-myosin activity to drive ratchet-like apical constriction. Nat Cell Biol 15:926-36|